Percutaneous, image-guided core needle biopsy is being increasingly used to diagnose breast cancer. Compared to surgical biopsy, this procedure is less invasive, less expensive, faster, minimizes deformity, leaves little or no scarring and requires a short time for recovery. However, core needle biopsy provides a limited sampling accuracy because only a few small pieces of tissue (for histology) are extracted from random locations in the suspicious mass. The long-term scientific aim of this project is to design a novel optical sensor based on near infrared (NIR) diffuse optical spectroscopy as an adjunct diagnostic modality to image-guided breast needle biopsy. The sensor will be able to augment breast biopsy procedures by: (1) surveying multiple sites without the need for tissue removal, (2) sampling a much larger volume of tissue than can actually be biopsied, and (3) providing accurate and immediate feedback of malignant tissue sites to biopsy. The goal of the work described in this proposal is to demonstrate the feasibility and effectiveness of our novel approach by pilot testing with numerical and synthetic breast tissue phantoms and by culminating with NIR diffuse optical spectroscopy of breast lesions in vivo in a pilot core needle biopsy study. The proposed work is based upon two central hypotheses: (a) there exists a systematic and significant difference in the NIR absorption and scattering properties of malignant and non-malignant (normal, benign) breast tissues, and (b) the NIR diffuse optical spectroscopy technique, which provides a quantitative measure of tissue absorption and scattering can be exploited as a highly sensitive and specific adjunct diagnostic modality to image-guided core needle biopsy. The specific aims of the proposed work are: (1) to investigate the feasibility and effectiveness of quantifying the absorption and scattering properties of numerical breast lesions of various shapes and sizes using an algorithm based on Diffusion theory, (2) to develop and test a first-generation hardware prototype and optical sensor for image-guided core needle biopsy, and (3) to investigate the effectiveness of our hardware prototype, optical sensor and Diffusion theory algorithm in a pilot core needle biopsy study. Successful completion of this project will provide for the first time, the proof-of-principle results to demonstrate the feasibility and effectiveness of NIR diffuse optical spectroscopy guided breast needle biopsy.